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Publication : Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus.

First Author  Mulvey B Year  2018
Journal  Cell Rep Volume  23
Issue  8 Pages  2225-2235
PubMed ID  29791834 Mgi Jnum  J:261850
Mgi Id  MGI:6158795 Doi  10.1016/j.celrep.2018.04.054
Citation  Mulvey B, et al. (2018) Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus. Cell Rep 23(8):2225-2235
abstractText  Preclinical work has long focused on male animals, though biological sex clearly influences risk for certain diseases, including many psychiatric disorders. Such disorders are often treated by drugs targeting the CNS norepinephrine system. Despite roles for noradrenergic neurons in behavior and neuropsychiatric disease models, their molecular characterization has lagged. We profiled mouse noradrenergic neurons in vivo, defining over 3,000 high-confidence transcripts expressed therein, including druggable receptors. We uncovered remarkable sex differences in gene expression, including elevated expression of the EP3 receptor in females-which we leverage to illustrate the behavioral and pharmacologic relevance of these findings-and of Slc6a15 and Lin28b, both major depressive disorder (MDD)-associated genes. Broadly, we present a means of transcriptionally profiling locus coeruleus under baseline and experimental conditions. Our findings underscore the need for preclinical work to include both sexes and suggest that sex differences in noradrenergic neurons may underlie behavioral differences relevant to disease.
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